This program project will emphasize the interaction of intrinsic aging processes related to lipid metabolism, carbohydrate metabolism, and connective tissue metabolism with the multifactoral diseases atherosclerosis, diabetes mellitus, and osteoporosis. Individual projects will involve predominately study of primates (human and monkeys) and will be focused on: a) factors controlling the transport of cholesterol rich and triglyceride-rich lipoproteins in plasma and into the arterial wall (particularly into aortic smooth muscle cells in tissue culture) in relation to aging and atherogenesis; b) the regulation of hormone secretion in relation to aging, altered lipid and carbohydrate metabolism, and atherosclerosis; c) the synthetic activities and metabolic responses of connective tissue cells in relation to aging, particularly protein synthesis by human fibroblasts and reactions of osteoclasts in relation to the pathogenesis of osteoporosis.